Many breast cancer cells (called estrogen receptor-positive breast cancers) require estrogen for survival. Women with these types of breast cancers are treated with drugs that that block estrogen, such as tamoxifen, fulvestrant, or aromatase inhibitors, causing the cells to die in a process called apoptosis. However, over time, these cancer cells learn to adapt and become resistant to this therapy.
"Tamoxifen and other estrogen inhibition drugs have been remarkably successful in the treatment of hormone-responsive breast cancers," said Jordan, vice president and scientific director for the medical science division at Fox Chase. "However, cancer cells are smart and they figure out how to survive these treatments. We believe we've become savvy to their art. Our laboratory study demonstrates that these same breast cancer cells die when we re-introduce them to estrogen." Jordan was the leader in the development of the use of tamoxifen to treat breast cancer. He holds the Alfred G. Knudson Jr., M.D., Ph.D., Chair in Cancer Research at Fox Chase.
The mechanism by which estrogen promotes apoptosis is not well understood. To understand this process, Jordan and his colleagues developed a line of breast cancer cells, called MCF-7:5C. These cells already are resistant to estrogen withdrawal. When the researchers treated MCF-7:5C cells with very small concentrations of estradiol they underwent apoptosis. The researchers also tested these cells in mice to see how this process might influence existing tumors. Again, the exposure to estradiol caused the cancer cells to die.
"These laboratory data have important clinical implications, particularly for the use of aromatase inhibitors as long-term therapy," write the authors, "and they suggest that, if and when resistance to aromatase inhibition occurs, a strategy of treatment with estrogen ... may be sufficient to kill the cancer and control disease progression."
Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu or call 1-888-FOX CHASE.